The CDC estimates that as many as 6.5 million Americans are living with Alzheimer’s disease. This number is projected to nearly triple to 14 million people by the year 2060. Alzheimer’s disease is the most common form of dementia that results in memory loss and cognitive impairment in the US.
A new study by a team of researchers from the Case Western Reserve University School of Medicine suggests a key protein molecule plays a major role in the accumulation of brain cholesterol, triggering the development of Alzheimer’s.
“Cholesterol accumulates in the brain and causes damage to the neuron—it’s long been understood as playing a role in Alzheimer’s disease pathology,” Qi said. “However, what causes the cholesterol accumulation in the brain continues to be unknown and could hold answers.”
The lab of Xin Qi, professor of physiology and biophysics at the School of Medicine, developed and patented a peptide inhibitor earlier in hopes of treating AD and Huntington’s disease. She said this study found that mice, when treated with the peptide inhibitor, demonstrated 50% restored memory function, based on testing such as navigating mazes.
The study, ATAD3A oligomerization promotes neuropathology and cognitive deficits in Alzheimer’s disease models, is the result of more than five years of research into the role of brain cholesterol and its relationship with AD. The researchers set out to answer two main questions:
- What role does brain cholesterol play in the disease?
- How can this new pathway be used for future treatment options?
Very little is known about how the protein functions within neurodegenerative diseases.
“In Huntington’s disease, the molecule ATAD3A becomes hyperactive and is oligomerized (repeated), which is a cause of the disease,” Qi said. “We worked with data scientists to see if ATAD3A also has a link to Alzheimer’s disease and, to our surprise, we found that the molecule is a top candidate linked to Alzheimer’s.”
The researchers gathered data by analyzing models and found a pathway linking ATAD3A and brain cholesterol. The researchers found that once ATAD3A forms repeating similar or identical parts through a process called oligomerization, it suppresses another protein called CYP46A1. The new protein then prevents cholesterol from being metabolized in the brain, meaning it accumulates. Researchers have linked the accumulation of brain cholesterol to disease progression in neurodegenerative diseases.
They found that ATAD3A—especially during oligomerization—could be the cause of AD development. With a possible target identified, Qi believes the next step to treatment lies in peptide inhibitors, which bind to ATAD3A and block it in action.
“Models treated with the peptide showed improved performance on the memory tests,” Qi said. “They showed increased memory retention, stronger cognitive activity and up to 50% restored damage to the memory.”
This means that targeting ATAD3A oligomerization can likely slow the progression of Alzheimer’s disease, Qi said. Further testing is underway.
The full study may be read here.
Photo by Pixabay.